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3D model of amphioxus steroid receptor complexed with estradiol
Michael E Baker1, David J Chang
1Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0693, USA. mbaker@ucsd.edu
Biochemical and Biophysical Research Communications
|June 23, 2009
Summary
Researchers explored the evolution of steroid receptors in amphioxus, a basal chordate. A 3D model revealed differences in estradiol binding, suggesting another steroid may regulate the amphioxus steroid receptor (SR).
Area of Science:
- Evolutionary biology
- Molecular endocrinology
- Structural biology
Background:
- The evolutionary origins of vertebrate steroid signaling remain incompletely understood.
- The discovery of an estrogen-binding steroid receptor (SR) in amphioxus, a basal chordate, offers insights into this evolutionary trajectory.
- Amphioxus shares a similar body plan with vertebrates, making its SR a key subject for comparative studies.
Purpose of the Study:
- To investigate the evolutionary history of estrogen-binding to steroid receptors.
- To construct and analyze a 3D model of the amphioxus SR complexed with estradiol.
- To elucidate the molecular basis for steroid-binding evolution in nuclear receptors.
Main Methods:
- Construction of a 3D structural model of the amphioxus steroid receptor (SR) in complex with estradiol.
- Comparative analysis of ligand-binding interactions between the amphioxus SR and human ERalpha.
- In silico prediction of the effects of specific mutations on steroid-binding affinity.
Main Results:
- The 3D model confirmed estradiol activation of the amphioxus SR.
- Key estradiol-binding interactions observed in human ERalpha are not conserved in the amphioxus SR, explaining estradiol's low affinity.
- Structural differences suggest a different physiological steroid regulator for the amphioxus SR.
Conclusions:
- The amphioxus SR exhibits distinct structural features compared to human ERalpha, impacting estradiol binding affinity.
- These findings suggest that the physiological ligand for amphioxus SR is likely not estradiol.
- A predicted mutation (Glu-346 to Gln) may enhance testosterone affinity, providing a model to study steroid-binding evolution in nuclear receptors.
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